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D. Kurosaka, K. Izumi, Y. Mashima, K. Tsubota; Involvement of Insulin–Like Growth Factor–I and Insulin–Like Growth Factor Binding Protein–3 in Corneal Fibroblasts During Corneal Wound Healing . Invest. Ophthalmol. Vis. Sci. 2006;47(13):5030.
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© ARVO (1962-2015); The Authors (2016-present)
Downstream messengers of transforming growth factor (TGF)–ß in differentiation of corneal fibroblasts into myofibroblasts were investigated. Effects of insulin–like growth factor (IGF)–I and insulin–like growth factor binding protein (IGFBP)–3 upregulated by TGF–ß were examined in human corneal fibroblasts and the possible involvement of IGF axis components in a mouse model of corneal wound healing was assessed.
Human corneal fibroblasts were incubated with TGF–ß2 or IGF–I to investigate IGF–I, IGF–II, IGFBP–3, type I collagen and α–smooth muscle action (α–SMA) mRNA as well as IGFBP–3 protein expression during myofibroblast differentiation. DNA synthesis was evaluated by 5–bromo–2’–deoxyuridine (BrdU) incorporation assay. IGFBP–3 mRNA expression, protein expression, and immunolocalization were investigated in mouse cornea after photorefractive keratectomy (PRK).
TGF–ß2 treatment induced IGF–I and IGFBP–3 mRNA as well as IGFBP–3 protein in human corneal fibroblasts. TGF–ß2 and IGF–I both stimulated expression of type I collagen. TGF–ß2 but not IGF–I potently stimulated α–SMA mRNA expression. IGF–I potently stimulated basal DNA synthesis, while IGFBP–3 inhibited it. IGF–I potently stimulated proliferation of TGF–ß2–activated myofibroblasts without reversing the activated fibrogenic phenotype, while IGFBP–3 suppressed IGF–I–induced proliferation of corneal fibroblasts. IGFBP–3 mRNA and protein increased in mouse corneas soon after PRK, when in vivo immunostaining of the corneas showed expression of IGFBP–3 in the deep layer of the corneal stroma.
These results suggest that during corneal wound healing, TGF–ß stimulates IGF axis components, while IGFBP–3 may modulate IGF–I–induced myofibroblast proliferation to suppress corneal mesenchymal overgrowth.
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